Skip to main content
Top
Published in: Endocrine 3/2019

01-12-2019 | Metastasis | Original Article

Identification of gene co-expression modules and hub genes associated with lymph node metastasis of papillary thyroid cancer

Authors: Tianyu Zhai, Dilidaer Muhanhali, Xi Jia, Zhiyong Wu, Zhenqin Cai, Yan Ling

Published in: Endocrine | Issue 3/2019

Login to get access

Abstract

Papillary thyroid cancer (PTC) is the most prevalent histological type among thyroid cancers, and some patients are at a high risk for recurrent disease or even death. Identification for the potential biomarkers of PTC may contribute to early discovery of recurrence and treatment. In The Cancer Genome Atlas (TCGA) database, we obtained the information of RNA sequence data and clinical characteristics of PTC. Weighted gene co-expression network analysis (WGCNA) was performed to construct gene co-expression networks and investigate the relationship between modules and clinical traits. Finally, we constructed 16 co-expression modules in 10,428 genes, and three key modules (darkturquoise, lightyellow, and red) associated with tumor N grade were identified. The results of functional annotation indicated that the darkturquoise module was primarily enriched in the regulation of the extracellular matrix (ECM), collagen metabolism, and cell adhesion, the lightyellow module was primarily enriched in the mitochondrial function regulation and energy synthesis, and the red module was primarily enriched in the process of cell junction, apoptosis, and inflammatory response, suggesting their significant role in the progression of PTC. In addition, the hub genes in the three modules were identified and screened for differentially expressed genes (DEGs). Relapse-free survival analyses found that 11 genes (KCNQ3, MET, FN1, ITGA3, RUNX1, ITGA2, PERP, GCSH, FAAH, NGFRAP1, and HSPA5) may play a pivotal role in PTC relapse. In general, our research revealed the key co-expression modules and identified several prognostic biomarkers, which provides some new insights into the lymph node metastasis of PTC.
Appendix
Available only for authorised users
Literature
4.
go back to reference D.S. McLeod, Current concepts and future directions in differentiated thyroid cancer. Clin. Biochem Rev. 31(1), 9–19 (2010)PubMedPubMedCentral D.S. McLeod, Current concepts and future directions in differentiated thyroid cancer. Clin. Biochem Rev. 31(1), 9–19 (2010)PubMedPubMedCentral
9.
go back to reference S. Ock, J. Ahn, S.H. Lee, H. M. Kim, H. Kang, Y.-K. Kim, Y.-K., H. Kook, W.J. Park, S. Kim, S. Kimura, C.K. Jung, M. Shong, M. Holzenberger, E. Dale Abel, T.J. Lee, B.Y. Cho, H.-S. Kim, J. Kim, Thyrocyte-specific deletion of insulin and IGF-1 receptors induces papillary thyroid carcinoma-like lesions through EGFR pathway activation. Int. J. Cancer 1–13 (2018). https://doi.org/10.1002/ijc.31779 CrossRef S. Ock, J. Ahn, S.H. Lee, H. M. Kim, H. Kang, Y.-K. Kim, Y.-K., H. Kook, W.J. Park, S. Kim, S. Kimura, C.K. Jung, M. Shong, M. Holzenberger, E. Dale Abel, T.J. Lee, B.Y. Cho, H.-S. Kim, J. Kim, Thyrocyte-specific deletion of insulin and IGF-1 receptors induces papillary thyroid carcinoma-like lesions through EGFR pathway activation. Int. J. Cancer 1–13 (2018). https://​doi.​org/​10.​1002/​ijc.​31779 CrossRef
16.
go back to reference G.J. Dennis, B.T. Sherman, D.A. Hosack, J. Yang, W. Gao, H.C. Lane, R.A. Lempicki, DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 4(5), P3–P14 (2003)CrossRef G.J. Dennis, B.T. Sherman, D.A. Hosack, J. Yang, W. Gao, H.C. Lane, R.A. Lempicki, DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 4(5), P3–P14 (2003)CrossRef
17.
go back to reference M. Ashburner, C.A. Ball, J.A. Blake, D. Botstein, H. Butler, J.M. Cherry, A.P. Davis, K. Dolinski, S.S. Dwight, J.T. Eppig, M.A. Harris, D.P. Hill, L. Issel-Tarver, A. Kasarskis, S. Lewis, J.C. Matese, J.E. Richardson, M. Ringwald, G.M. Rubin, G. Sherlock, Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat. Genet 25(1), 25–29 (2000). https://doi.org/10.1038/75556 CrossRefPubMedPubMedCentral M. Ashburner, C.A. Ball, J.A. Blake, D. Botstein, H. Butler, J.M. Cherry, A.P. Davis, K. Dolinski, S.S. Dwight, J.T. Eppig, M.A. Harris, D.P. Hill, L. Issel-Tarver, A. Kasarskis, S. Lewis, J.C. Matese, J.E. Richardson, M. Ringwald, G.M. Rubin, G. Sherlock, Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat. Genet 25(1), 25–29 (2000). https://​doi.​org/​10.​1038/​75556 CrossRefPubMedPubMedCentral
25.
go back to reference K. Rue-Albrecht, P.A. McGettigan, B. Hernández, N.C. Nalpas, D.A. Magee, A.C. Parnell, S.V. Gordon, D.E. MacHugh, GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data. BMC Bioinform. 17(1), 126–138 (2016). https://doi.org/10.1186/s12859-016-0971-3 CrossRef K. Rue-Albrecht, P.A. McGettigan, B. Hernández, N.C. Nalpas, D.A. Magee, A.C. Parnell, S.V. Gordon, D.E. MacHugh, GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data. BMC Bioinform. 17(1), 126–138 (2016). https://​doi.​org/​10.​1186/​s12859-016-0971-3 CrossRef
29.
go back to reference S.-T. Tsai, T.-Y. Wong, C.-Y. Ou, S.-Y. Fang, K.-C. Chen, J.-R. Hsiao, C.-C. Huang, W.-T. Lee, H.-I. Lo, J.-S. Huang, J.-L. Wu, C.-J. Yen, W.-T. Hsueh, Y.-H. Wu, M.-W. Yang, F.-C. Lin, J.-Y. Chang, K.-Y. Chang, S.-Y. Wu, H.-C. Liao, C.-L. Lin, Y.-H. Wang, Y.-L. Weng, H.-C. Yang, J.S. Chang, The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer. Int. J. Cancer 135(10), 2424–2436 (2014). https://doi.org/10.1002/ijc.28885 CrossRefPubMed S.-T. Tsai, T.-Y. Wong, C.-Y. Ou, S.-Y. Fang, K.-C. Chen, J.-R. Hsiao, C.-C. Huang, W.-T. Lee, H.-I. Lo, J.-S. Huang, J.-L. Wu, C.-J. Yen, W.-T. Hsueh, Y.-H. Wu, M.-W. Yang, F.-C. Lin, J.-Y. Chang, K.-Y. Chang, S.-Y. Wu, H.-C. Liao, C.-L. Lin, Y.-H. Wang, Y.-L. Weng, H.-C. Yang, J.S. Chang, The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer. Int. J. Cancer 135(10), 2424–2436 (2014). https://​doi.​org/​10.​1002/​ijc.​28885 CrossRefPubMed
35.
go back to reference S. Fan, Y.X. Ma, J.A. Wang, R.Q. Yuan, Q. Meng, Y. Cao, J.J. Laterra, I.D. Goldberg, E.M. Rosen, The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3’ kinase. Oncogene 19(18), 2212–2223 (2000). https://doi.org/10.1038/sj.onc.1203566 CrossRefPubMed S. Fan, Y.X. Ma, J.A. Wang, R.Q. Yuan, Q. Meng, Y. Cao, J.J. Laterra, I.D. Goldberg, E.M. Rosen, The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3’ kinase. Oncogene 19(18), 2212–2223 (2000). https://​doi.​org/​10.​1038/​sj.​onc.​1203566 CrossRefPubMed
47.
go back to reference I.A. Khan, B.H. Yoo, O. Masson, S. Baron, D. Corkery, G. Dellaire, L.D. Attardi, K.V. Rosen, ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells. Oncogene 35(44), 5759–5769 (2016). https://doi.org/10.1038/onc.2016.109 CrossRef I.A. Khan, B.H. Yoo, O. Masson, S. Baron, D. Corkery, G. Dellaire, L.D. Attardi, K.V. Rosen, ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells. Oncogene 35(44), 5759–5769 (2016). https://​doi.​org/​10.​1038/​onc.​2016.​109 CrossRef
51.
go back to reference H.A. Chen, Y.W. Chang, C.F. Tseng, C.F. Chiu, C.C. Hong, W. Wang, M.Y. Wang, M. Hsiao, J.T. Ma, C.H. Chen, S.S. Jiang, C.H. Wu, M.C. Hung, M.T. Huang, J.L. Su, E1A-mediated inhibition of HSPA5 suppresses cell migration and invasion in triple-negative breast cancer. Ann. Surg. Oncol. 22(3), 889–898 (2015). https://doi.org/10.1245/s10434-014-4061-3 CrossRefPubMed H.A. Chen, Y.W. Chang, C.F. Tseng, C.F. Chiu, C.C. Hong, W. Wang, M.Y. Wang, M. Hsiao, J.T. Ma, C.H. Chen, S.S. Jiang, C.H. Wu, M.C. Hung, M.T. Huang, J.L. Su, E1A-mediated inhibition of HSPA5 suppresses cell migration and invasion in triple-negative breast cancer. Ann. Surg. Oncol. 22(3), 889–898 (2015). https://​doi.​org/​10.​1245/​s10434-014-4061-3 CrossRefPubMed
52.
go back to reference D. Fiore, M.C. Proto, S. Pisanti, P. Picardi, A.C. Pagano Zottola, S. Butini, S. Gemma, A. Casagni, C. Laezza, M. Vitale, A. Ligresti, V. Di Marzo, D.M. Zisterer, S. Nathwani, D.C. Williams, G. Campiani, P. Gazzerro, M. Bifulco, Antitumor effect of pyrrolo-1,5-benzoxazepine-15 and its synergistic effect with Oxaliplatin and 5-FU in colorectal cancer cells. Cancer Biol. Ther. 17(8), 849–858 (2016). https://doi.org/10.1080/15384047.2015.1078028 CrossRefPubMed D. Fiore, M.C. Proto, S. Pisanti, P. Picardi, A.C. Pagano Zottola, S. Butini, S. Gemma, A. Casagni, C. Laezza, M. Vitale, A. Ligresti, V. Di Marzo, D.M. Zisterer, S. Nathwani, D.C. Williams, G. Campiani, P. Gazzerro, M. Bifulco, Antitumor effect of pyrrolo-1,5-benzoxazepine-15 and its synergistic effect with Oxaliplatin and 5-FU in colorectal cancer cells. Cancer Biol. Ther. 17(8), 849–858 (2016). https://​doi.​org/​10.​1080/​15384047.​2015.​1078028 CrossRefPubMed
Metadata
Title
Identification of gene co-expression modules and hub genes associated with lymph node metastasis of papillary thyroid cancer
Authors
Tianyu Zhai
Dilidaer Muhanhali
Xi Jia
Zhiyong Wu
Zhenqin Cai
Yan Ling
Publication date
01-12-2019
Publisher
Springer US
Published in
Endocrine / Issue 3/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-02021-9

Other articles of this Issue 3/2019

Endocrine 3/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.